PMID: 9553060

Szabo K, Welker E, Bakos, Muller M, Roninson I, Varadi A, Sarkadi B
Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. Cooperation of the nucleotide binding domains.
J Biol Chem. 1998 Apr 24;273(17):10132-8., 1998-04-24 [PubMed]
Sentences
No. Mutations Sentence Comment
5 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:5:134
status: NEW
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ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:5:152
status: NEW
view ABCB1 p.Lys1076Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:5:127
status: NEW
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ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:5:146
status: NEW
view ABCB1 p.Lys433Met details
MDR1 variants with mutations of key lysine residues to methionines in the N-terminal or C-terminal nucleotide binding domains (K433M, K1076M, and K433M/K1076M), which bind but do not hydrolyze ATP, do not show nucleotide trapping either with or without the transported drug substrates. Login to comment
39 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:39:177
status: NEW
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ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:39:195
status: NEW
view ABCB1 p.Lys1076Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:39:170
status: NEW
view ABCB1 p.Lys433Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:39:189
status: NEW
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Baculovirus transfer vectors were constructed as described earlier (20, 21) by using the human MDR1 cDNA encoding a protein with the following mutants: ⌬aa 78-97, K433M, K1076M, and K433M/K1076M. Login to comment
117 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:117:118
status: NEW
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ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:117:157
status: NEW
view ABCB1 p.Lys1076Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:117:80
status: NEW
view ABCB1 p.Lys433Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:117:151
status: NEW
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These lysines were replaced by methionines either in the N-terminal ABC domain (K433M), in the C-terminal ABC domain (K1076M), or in both ABC domains (K433M/K1076M). Login to comment
125 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:125:223
status: NEW
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ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:125:242
status: NEW
view ABCB1 p.Lys1076Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:125:216
status: NEW
view ABCB1 p.Lys433Met details
ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:125:235
status: NEW
view ABCB1 p.Lys433Met details
Nucleotide trapping in the nucleotide binding site mutants of MDR1. Labeling was performed in Sf9 cell membranes expressing either beta-galactosidase, the wild-type human MDR1, or the nucleotide binding site mutants K433M, K1076M, and K433M/ K1076M. Login to comment
135 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:135:77
status: NEW
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ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:135:68
status: NEW
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As shown, there was no significant azido-ATP trapping in either the K433M or K1076M mutant MDR1 proteins, whereas the corresponding immunoblots ensured that the isolated Sf9 cell membranes contained about equal amounts of the MDR1 variants in all experiments. Login to comment
162 ABCB1 p.Lys1076Met
X
ABCB1 p.Lys1076Met 9553060:162:73
status: NEW
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ABCB1 p.Lys433Met
X
ABCB1 p.Lys433Met 9553060:162:57
status: NEW
view ABCB1 p.Lys433Met details
The mutant MDR1 proteins, in which lysines in the first (K433M), second (K1076M), or both nucleotide binding domains are replaced by methionines, were demonstrated to bind MgATP less efficiently at low MgATP concentrations (2-5 ␮M) but similarly to the wild-type MDR1 at concentrations above 10 ␮M MgATP (21). Login to comment